Cytoplasmic Receptors for Glucocoeticoids in Intestine of Suckling Rats

Kenning, Susan J; Ballard, Pl; Kretchmer, Norman

doi:10.1203/00006450-197404000-00250

Cited by 15 publications

(21 citation statements)

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“…Although developmental changes in glucocorticoid receptor density would provide a possible explanation for the increased maximal responsiveness, a study in rat demonstrated that the receptor abundance does not increase from the 1st to the 2nd postnatal week (44). The observed increases in steady state levels of trehalase mRNA and sucraseisomaltase mRNA could reflect an influence of age on either gene transcription or mRNA stability.…”

Section: Discussionmentioning

confidence: 99%

Development of Glucocorticoid-Responsiveness in Mouse Intestine

et al. 2001

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There are conflicting data from human studies regarding the ability of exogenous glucocorticoids to stimulate maturation of the small intestine. The discrepancies may relate to differences in hormone doses and age administered. To explore this general concept, we have used a mouse model to determine intestinal responsiveness to dexamethasone (DEX) at various times during development. We first showed that trehalase mRNA is a sensitive marker of intestinal maturation in the mouse; being undetectable (by Northern blotting) in the prenatal period, expressed at low levels during the first 2 postnatal weeks and then displaying a marked increase in the 3rd postnatal week. DEX was unable to elicit detectable trehalase mRNA in fetal mice, but caused significant increases in the postnatal period. The use of a range of DEX doses (0.0125-2.5 nmol/g BW per day) established that there is no change in sensitivity between the 1st and 2nd postnatal weeks, but there is a significant increase in maximal responsiveness of trehalase mRNA to the hormone. Similar results were obtained when sucrase-isomaltase mRNA was assayed in the same animals. Thus, in this rodent model, there appears to be at least three phases in the DEX responsiveness of the developing intestine: an early phase (prenatal) when DEX is unable to elicit intestinal maturation; then a phase (first postnatal week) of modest responsiveness; then a transition to increased responsiveness. These findings point to the need for careful attention to dose and age in analyses of glucocorticoid effects in human infants. Glucocorticoids have become an important component in the pharmacologic treatment of prematurity because of their maturational effects on certain tissues. In the lung, for example, corticosteroid therapy is central to the prevention of respiratory distress syndrome. Interestingly, several clinical trials using exogenous glucocorticoids in the treatment of prematurity also demonstrated a decreased incidence of necrotizing enterocolitis (NEC) in steroid-treated infants (1-3). In addition, Halac and coworkers conducted a prospective human study of the effect of DEX on the incidence of NEC and found a significant reduction in NEC among neonates receiving either prenatal or postnatal steroid (4). As NEC is typically associated with immaturity (5-7), these findings suggest that exogenous glucocorticoid may exert a maturational effect on the intestine. However, not all trials observed decreased NEC (2). Likewise, although investigators have found significant maturation of intestinal motility (8) and permeability (9) in premature infants whose mothers received prenatal glucocorticoid, another study reported no effect on lactase maturation (10). The latter in vivo observation is in contrast to several studies that have shown elevation of lactase activity in response to glucocorticoid treatment in explant cultures of human fetal intestine (11-13). We hypothesize that such seemingly disparate results may be explained by differences in dosages and timing of corticosteroid tr...

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Section: Discussionmentioning

confidence: 99%

Development of Glucocorticoid-Responsiveness in Mouse Intestine

et al. 2001

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“…However the problem with this supposition has been that the majority of the reported values for plasma corticosterone during development are uniformly high from the second through the third postnatal week (66)(67)(68)(69)(70). We raised the question of why the high concentrations of endogenous corticosterone did not elicit intestinal changes during the second week of life and proposed (57,71) that the timing of glucocorticoid action in this system must reflect increased responsiveness of the target cells at the beginning of the third postnatal week. However, when the cytoplas- mic receptors for glucocorticoids in the jejunum were assayed throughout the developmental period they were found to be present in higher concentrations during the first and second postnatal week than during the third week (71), thus failing to provide a basis for increasing responsiveness.…”

Section: Role Of Hormonesmentioning

confidence: 99%

“…We raised the question of why the high concentrations of endogenous corticosterone did not elicit intestinal changes during the second week of life and proposed (57,71) that the timing of glucocorticoid action in this system must reflect increased responsiveness of the target cells at the beginning of the third postnatal week. However, when the cytoplas- mic receptors for glucocorticoids in the jejunum were assayed throughout the developmental period they were found to be present in higher concentrations during the first and second postnatal week than during the third week (71), thus failing to provide a basis for increasing responsiveness. Since circulating concentrations of thyroxine are known to increase considerably between postnatal days 10 and 16 (72)(73)(74)(75) we have investigated the possibility that this hormone synergizes with glucocorticoids and thereby explains the timing of the glucocorticoid-mediated changes in the intestine (76).…”

Section: Role Of Hormonesmentioning

confidence: 99%

Biochemistry of Intestinal Development

Henning¹

1979

Environmental Health Perspectives

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In biochemical terms, the rat small intestine is relatively immature at birth and for the first two postnatal weeks. Then during the third week a dramatic array ofenzymic changes begins, and by the end ofthe fourth week the intestine has the digestive and absorptive properties of the adult. Selective examples of these changes are discussed with emphasis on their implications for toxicological studies. The review also includes a detailed consideration of the roles of the dietary change of weaning and of glucocorticoid and thyroid hormones in the regulation of intestinal development.My aim in this paper is to use the rat as a model system for a discussion of the postnatal development of small intestinal function. Factors which affect the developmental process will be reviewed in terms of their implications for toxicological studies. Morphologic Development of the IntestineBy the time of birth, the intestinal mucosa of the rat displays a high level of structural development characterized by villi lined with a single layer of columnar epithelial cells which have well-defined microvilli at their absorptive surface (1-3). After birth, continuous proliferation of epithelial cells occurs only in the lower regions of the crypts (4, 5), and cells migrate from there onto and along the villi, eventually being extruded from the tips into the lumen of the intestine. In adult rats and mice the generation time for the crypt cells is 10-14 hr (6), and the transit time along the length of the villus is approximately 48 hr (7). The characteristics of proliferation and migration of enterocytes in adult animals are dealt with in detail in the review by Lipkin (8). In neonatal rats, generation and migration of the cells is much slower than in adults. Despite the fact that the neonatal villi are shorter, the transit time is at least % hr (7, 9). During the third postnatal week there are significant changes in both cell kinetics and mor-

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“…Specific binding of 3H-dcxamethasonc was calculat ed by subtracting the dpm/mg protein obtained in the presence of nonlabeled dexametha sone from that in its absence. Further details of the method are described elsewhere [12].…”

Section: Methodsmentioning

confidence: 99%

“…Such an increase could allow progressively more hydrocortisone to be transported to the nuclei of the re sponsive population of cells and thus conceivably cause a greater inductive effect. To test this hypothesis, a method was devised for quantitative assay of cytoplasmic receptor macromolecules having high affinity and specificity for glucocorticoids [12]. When the concentration of these macromolecules was determined in intestinal tissue derived from animals at various ages from late fetal to adult (fig.…”

Section: H Enning/h Flman/k Retchmermentioning

confidence: 99%

Studies on Normal and Precocious Appearance of Jejunal Sucrase in Suckling Rats

Henning

Helman

Kretchmer³

1975

Neonatology

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Some of the cellular and molecular events involved in the normal and precocious appearance of sucrase in jejunum of infant rats have been studied. Actinomycin D has been shown to inhibit (by 79%) the rise in sucrase activity usually seen after administration of hydrocortisone to 9-day-old rats. The precocious appearance of sucrase has also been studied with respect to the cytological localization of enzyme activity in the intestinal mucosa. Tissue was sectioned in a cryostat (transverse to the villi) and sucrase was assayed in homogenates prepared from the sections. By 24 h after administration of hydrocortisone to 9-day-old animals, sucrase was detectable only at the bases of the villi. During the subsequent 72 h the enzyme activity increased and spread along the villi at a rate consistent with that of cell migration. These data have lead to the conclusion that the action of glucocorticoids on enterocytes can occur only when the cells are in their proliferative phase. An ontogenic study of the ability of hydrocortisone to elicit jejunal sucrase showed that the tissue becomes increasingly responsive to the hormone with increasing age through the first and second postnatal weeks. Various hypotheses to explain this increase have been examined.

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Cytoplasmic Receptors for Glucocoeticoids in Intestine of Suckling Rats

Cited by 15 publications

References 0 publications

Development of Glucocorticoid-Responsiveness in Mouse Intestine

Development of Glucocorticoid-Responsiveness in Mouse Intestine

Biochemistry of Intestinal Development

Studies on Normal and Precocious Appearance of Jejunal Sucrase in Suckling Rats

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